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• Nervous system dysfunction + Seizures
  (urine alkalinization may prevent rhabdo induced AKI)

• ?Pulmonary tuberculosis

Haemostasis

How to read this diagram:

1. The quickest response to endothelial damange is formation of the platelet plug. Platelets roll off the exposed collagen and stick to it.
   1. The platelets bind to collagen - adhesion
   2. secrete their granules - activation
   3. bind to each other - aggregation
2. Platelets form the primary haemostatic plug within about 1 minute. This needs to be stabilized by the coagulation cascade proteins.

Formation of the primary platelet plug

coagulation cascade and assessment

[!INFO] Assessment of coagulation
PT - Extrinsic and common pathways
aPTT - Intrinsic and common pathways

vW disease

vWF is made by endothelium.
Roles:

1. Platelet adhesion + aggregation (see [[#Formation of the primary platelet plug]]) -> Intrinsic pathway defect -> Prolonged APTT
2. Transport of factor VIII. -> Low factor VIII levels

Commonest inherited bleeding disorder; usually autosomal dominant.
Mucosal bleeding.

Antiphospholipid syndrome - APS

Anticoagulants

Source

Heparin induced thrombocytopaenia

Arises because heparin stimulates HIT antibody production.
Antibodies bind to PF4 on the platelet surface and stimulate platelet activation.

This results in thrombocytopaenia (platelets found to to antibodies are removed by the Reticuloendothelial system) - commonest manifestation.
Associated thrombosis (venous more than arterial) - around 50%, if untreated. Manifestations include pulmonary embolism, skin necrosis, limb gangrene. Arterial thrombi (MI, stroke) can also occur.

Bleeding is rare.

Onset is 5 - 10 days after onset of therapy.
Risk Heparin > fractionated heparin
High dose > low dose

"4 T" score is used to assess the likelihood of HIT.
Treatment: Stop heparin and start non heparin anti-coagulation

[!INFO] SUMMARY
Leukemia and Lymphoma are both cancers that are not associated with a tumor.
Lymphomas are cancers that affect the lymph system and start in cells called lymphocytes. They are divided into Non-Hodgkin and Hodgkin lymphomas.

Leukemia is a cancer of the early blood-forming tissues, including your bone marrow and lymph system.

Leukemia typically involves white blood cells, the cells that are your infection fighters. Leukemia can be divided into categories: fast growing (acute) and slow growing (chronic); and by which white blood cells are affected.

• Acute lymphocytic leukemia (ALL) is the most common type of leukemia in young children and can also occur in adults.
• Acute myelogenous leukemia (AML) is a common type of acute leukemia, more common in adults but can occur in children as well.
• Chronic lymphocytic leukemia (CLL) is the most common chronic adult leukemia, you may feel well for years without needing treatment.
• Chronic myelogenous leukemia (CML) mainly affects adults. A person with CML may have few or no symptoms for months or years before entering a phase in which the leukemia cells grow more quickly.
• There are other, rarer types of leukemia, including hairy cell leukemia, myelodysplastic syndromies and myeloproliferative disorders.
  Source


*painless*, *rubbery*, cervical lymph node is the commonest presentation. 

[!TIP] Hodgkin's : Reed sternberg cell +, younger patient, slightly better survival

Fetal hemoglobin (Hb F; alpha2gamma2)
HbA2 (α2δ2)

Overall summary:
Beta thal major: has a lot of HbF
Thal trait = minor = very little HbF

As seen in the 'heterozygous' column, if there is at least one properly functioning beta gene, there will be very little HbF. "Mnemonic: The disease is not sever enough for the body to switch over to HbF production."

As seen in the table.below, thalassemia "trait" = heterozygous mutation

more terminology: intermedia and trait

Source

Typical beta thalassemia trait investigation results: pastest Answers

++ /dev/null

Malaria red cell entry receptors:

Plasmodium falciparum invades human erythrocytes by redundant pathways
Unlike P. vivax that has one Duffy Binding-Like (DBL) receptor, P. falciparum has four members of the DBL receptor family.

CT

Causes of increased CPK

#2022BSQ Q31
CPK = CK.
Creatine Kinase is a catalyst for the formation of ATP from ADP via transfer of phosphate from creatine phosphate (which is an energy reservoir for muscle.
It is a very good indicator of muscle breakdown and it's progression.
CPK is eleminated by the Reticuloendothelial system. Serum level isn't elevated in kidney disease.

3 isoforms

• Skeletal muscle - 99% CK MM

• CK-MB = Usually in cardiac muscle. Can also be elevated in elite athletes and normal people after strenuous exercise (i.e can produce false +ve for MI)

• CK is usually elevated in myopathies. => there are different types of myopathies

  • Inflammatory myopathies - polymyositis / dermatomyositis
  • Drugs - colchicine (gout), antimalarials, statins, alcohol
  • Metabolic myopathies - carnitine palmitoyltransferase deficiency, Muscle phosphorylase deficiency (McArdle's disease)
    • McArdles disease - Autosomal recessive, exercise intolerance in childhood followed by cramps and myoglobinuria
  • Endocrine myopathies - hypothyroidism, acromegaly
  • Periodic paralyses - hours to days of muscle weakness with sharp rises of CPK; due to muscle membrane refractoriness secondary to ion shifts.
  • Neuroleptic malignant syndrome
  • Malignant hyperthermia - usually follows use of anaesthetic agents.

• Can also be elevated in a few non myopathic conditions

  • Exercise
  • Iatrogenic muscle injury
  • motor neuron disease
  • Asymptomatic elevation in CK

Urine cultures

We went to get urine samples which contain bacteria which have managed to enter the bladder. (bacteria colonize the distal urethra and genital mucosa)
Theoretical best sample is first voided urine of the day as bacteria have had time to multiply overnight and it is also the most concentrated sample.
Suprapubic taps should yield sterile urine in a healthy patient.

Prostatic massage should be done prior to urine sample correction in suspected if chronic bacterial prostatis is suspected. Massage should be avoided in acute bacterial prostatits -> risk of bactiraemia!

Sample is cooled until it is send to the lab to prevent bacterial multiplication affecting the colony count.

Urine microscopye

pyuria

8 cells / microL = 2-5 cells per High power Field.
Very high associated with urinary infection.

• bacteuria without pyuria -> usually means colonization rather than infection. (unless of course, patient is symptomatic)

White blood cell casts - renal infection = could be pyelonephritis.

Causes of sterile pyuria:

• False -ve for bacteria
  • Contamination with antiseptic
  • Atypical pathogens - Chlamydia, Ureaplasma urealyticum, or tuberculosis
• False +ve for leukocytes
  • Contamination with vaginal leukocytes
  • Chronic intersitial nephritis
  • Nephrolithiasis
  • Uroepithial tumour
  • Intrabdominal inflammation adjacent to the bladder

• BCG vaccination only prevents CNS TB and disseminated TB.
• Sputum smear : positive only in post primary TB or cavitatory TB